The primary goal of the current proposal is to obtain empirical, neurobiological evidence supporting the validity of hypotheses of sensitization and dopamine (DA) deficiency in human cocaine abusers based on SPECT measurements of brain DA function. The specific aims proposed are: #1 to determine whether cocaine addicts demonstrate a sensitized response to amphetamine as evidenced by an increased displacement of D2 radiotracer {123I]IBMZ compared to age-and gender-matched healthy control subjects: #2 to determine whether cocaine addicts have reduced basal levels of extracellular DA as evidenced by a smaller increase in [123I]IBMZ binding potential after DA depletion by the tryosine hydorxylase inhibitor, alpha-methyl-para-tryosine (AMPT) compared to age- and gender-matched healthy control subjects. We have recently acquired preliminary data assessing amphetamine-induced reductions in [123I]IBMZ V3 in 4 cocaine addicts and 4 healthy controls. Although the limited size of our sample populations precluded formal statistical comparisons, these preliminary results are consistent with the hypothesis that cocaine addicts have a sensitized neurochemical response to amphetamine.